What Is the Comparative Ability of 18F-FDG PET/CT, 99mTc-MDP Skeletal Scintigraphy, and Whole-body MRI as a Staging Investigation to Detect Skeletal Metastases in Patients with Osteosarcoma and Ewing Sarcoma?

Abstract

Background: Skeletal metastases of bone sarcomas are indicators of poor prognosis. Various imaging modalities are available for their identification, which include bone scan, positron emission tomography/CT scan, MRI, and bone marrow aspiration/biopsy. However, there is considerable ambiguity regarding the best imaging modality to detect skeletal metastases. To date, we are not sure which of these investigations is best for screening of skeletal metastasis.

Question/purpose: Which staging investigation-18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT), whole-body MRI, or 99mTc-MDP skeletal scintigraphy-is best in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in detecting skeletal metastases in patients with osteosarcoma and those with Ewing sarcoma?

Methods: A prospective diagnostic study was performed among 54 of a total 66 consecutive osteosarcoma and Ewing sarcoma patients who presented between March 2018 and June 2019. The institutional review board approved the use of all three imaging modalities on each patient recruited for the study. Informed consent was obtained after thoroughly explaining the study to the patient or the patient's parent/guardian. The patients were aged between 4 and 37 years, and their diagnoses were proven by histopathology. All patients underwent 99mTc-MDP skeletal scintigraphy, 18F-FDG PET/CT, and whole-body MRI for the initial staging of skeletal metastases. The number and location of bone and bone marrow lesions diagnosed with each imaging modality were determined and compared with each other. Multidisciplinary team meetings were held to reach a consensus about the total number of metastases present in each patient, and this was considered the gold standard. The sensitivity, specificity, PPV, and NPV of each imaging modality, along with their 95% confidence intervals, were generated by the software Stata SE v 15.1. Six of 24 patients in the osteosarcoma group had skeletal metastases, as did 8 of 30 patients in the Ewing sarcoma group. The median (range) follow-up for the study was 17 months (12 to 27 months). Although seven patients died before completing the minimum follow-up, no patients who survived were lost to follow-up.

Results: With the number of patients available, we found no differences in terms of sensitivity, specificity, PPV, and NPV among the three staging investigations in patients with osteosarcoma and in patients with Ewing sarcoma. Sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 67% (4 of 6 [95% CI 22% to 96%]) and specificities were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 78% (14 of 18 [95% CI 52% to 94%]), respectively, in patients with osteosarcoma. In patients with Ewing sarcoma, sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 88% (7 of 8 [95% CI 47% to 100%]), 88% (7 of 8 [95% CI 47% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and specificities were 100% (22 of 22 [95% CI 85% to 100%]), 95% (21 of 22 [95% CI 77% to 100%]), and 95% (21 of 22 [95% CI 77% to 100%]), respectively. Further, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and the NPVs were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 88% (14 of 16 [95% CI 62% to 98%]), respectively, in patients with osteosarcoma. Similarly, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (7 of 7 [95% CI 59% to 100%]), 88% (7 of 8 [95% CI 50% to 98%]), and 80% (4 of 5 [95% CI 28% to 100%]), and the NPVs were 96% (22 of 23 [95% CI 78% to 100%]), 95% (21 of 22 [95% CI 77% to 99%]), and 84% (21 of 25 [95% CI 64% to 96%]), respectively, in patients with Ewing sarcoma. The confidence intervals around these values overlapped with each other, thus indicating no difference between them.

Conclusion: Based on these results, we could not demonstrate a difference in the sensitivity, specificity, PPV, and NPV between 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy for detecting skeletal metastases in patients with osteosarcoma and Ewing sarcoma. For proper prognostication, a thorough metastatic workup is essential, which should include a highly sensitive investigation tool to detect skeletal metastases. However, our study findings suggest that there is no difference between these three imaging tools. Since this is a small group of patients in whom it is difficult to make broad recommendations, these findings may be confirmed by larger studies in the future.

Level of evidence: Level II, diagnostic study.

Fig. 1.

A Standards for Reporting of Diagnostic Accuracy Studies (STARD) flow diagram that demonstrates patient recruitment during the study period.

Fig. 2.

A-D These (A) anterior-view and (B) posterior-view ^99mTc-MDP whole-body bone scan images are from an 11-year-old girl with Ewing sarcoma of the right distal femur and show heterogeneous radiotracer uptake in a mass in the right distal femur with no other metastatic lesion (false-negative bone scan). (C) A maximum-intensity projection of an ¹⁸F-FDG PET/CT scan shows heterogeneous uptake in a large expansile mass in the right distal thigh along with increased uptake suggesting a metastasis in the left scapula; left proximal humerus; D11, D12, and L4 vertebrae; left ilium; right ischium; right acetabulum; and right proximal tibia. (D) An inverted (negative) image of a coronal diffusion-weighted whole-body MR image of the same patient shows a hypointense lesion in the right distal femur and surrounding soft tissues of the distal thigh, suggestive of a primary tumor, along with metastases in the left scapula, left proximal humerus, D12 and L4 vertebrae, left ilium, right ischium, right acetabulum, and right proximal tibia. It only failed to detect one metastatic lesion of the D11 vertebra compared with ¹⁸F-FDG PET/CT.

Fig. 3.

A-H These transaxial fused ¹⁸F-FDG PET/CT images from a 10-year-old boy with Ewing sarcoma of the right fibula demonstrate areas of increased FDG uptake in the (A) shaft of the right femur, (B) left sacral ala, (C) left head of the femur, and (D) left iliac bone, suggesting metastatic lesions. Transaxial fused ¹⁸F-FDG PET/CT images of this patient at the same four levels 5 months after chemotherapy demonstrate decreased FDG uptake in the (E) shaft of the right femur, (F) left sacral ala, (G) left head of the femur, and (H) left iliac bone, which were previously showing high FDG uptake, confirming that these lesions were actually skeletal metastases from the primary tumor. This also gave us information that the tumor was responding to the given chemotherapeutic regimen, highlighting the utility of ¹⁸F-FDG PET/CT in assessing the patient’s response to treatment.

Fig. 4.

A-D (A) A ^99mTc-MDP whole-body bone scan of a 10-year-old boy with an osteosarcoma of the left distal femur shows increased uptake in the ipsilateral proximal tibia, suggesting a metastatic lesion (arrow). (B) A maximum-intensity projection of an ¹⁸F-FDG PET scan shows heterogeneous radiotracer uptake in the distal part of the left thigh (primary tumor), with no other areas of abnormal radiotracer uptake. (C) A coronal short tau inversion recovery whole-body MR image of the same patient shows a lesion in the left proximal tibia. However, this lesion had an altered signal intensity, dissimilar to the primary lesion in the distal femur. (D) An additional T2-weighted spin-echo-sequence MRI of the left knee was performed in which the proximal tibia lesion was confirmed to be an enchondroma, rather than an osseous metastasis from the primary tumor.

Fig. 5.

This flow chart shows the study protocol.